Some plants are known to not be infected by pathogens, apparently because of the presence of effective antimicrobials and inhibitors of pumps that excrete them. In the last sense, by increasing the concentration of antimicrobials within the microorganism, resistance can be reversed. Emulation of nature´s strategy can be a valuable tool against resistant microorganisms in the human being. In this context, we report some own findings concerning 2?, 4?-dihydroxy-5?-(1???, 1???-dimethylallyl)-6-prenylpinocembrin (6PP), a prenylated flavonoid isolated and identified from the argentine plant Dalea elegans. In previous works, it had showed activity against multi-resistant Staphylococcus aureus and Candida albicans. It had also demonstrated uncoupling effect on mitochondria and anti-oxidant activity. It appeared to be safe, according to in vivo studies on acute toxicity including LD50 values. 6PP inhibited the efflux of rhodamine 6G (Rh 6G) in C. albicans resistant to azoles (R Ca) that expresses transporters of CDR1, CDR2 and MDR1 type. When inhibition was compared to fluconazole (Flz) the parameters were, for 6PP and Flz, respectively, maximum inhibition: 45.46% and 41.42%; apparent KI 42.95 µM and 107.81 µM.
The effect of fluconazole on RCa cell growth, Rh 6G efflux and antifungal activity of 6PP was studied when the mentioned azole was added into culture medium. At concentrations between 3 and 13 µM, Flz did not modify either the growth of R Ca or the effect of 6PP on Rh 6G efflux. 6PP inhibited fungal growth in absence or in presence of 13 µM flz. The results are consistent with the expression of constitutive efflux pumps and a dual action of 6PP: inhibition of azole transporters and antifungal effect on R C.a.
A combined therapy of 6PPwith azoles could improve the treatment, by returning the efficacy of the antimycotic drugs through inhibition of their efflux. This action would be relevant since mycosis, especially those produced by C. albicans, play an important role in inmunosuppressed patients, particularly with the advent of AIDS.
